Alpha Psychiatry 2021;22(1):67-69 Alpha Psychiatry DOI: 10.5455/apd.114069

Manic Episode as a Result of Adding to a Patient under Treatment

ABSTRACT

Antidepressants with effects can often be added to treatment for prob- lems emerging in patients receiving treatment. One of these is trazodone, which is an antidepressant that exhibits hypnotic effect by the effect of H1 re- ceptor antagonist and 5-HT2A stimulation, which is a transporter protein inhib- itor and 5-HT2A and 5HT2C antagonist. Some can cause -like mood episodes when used singly or in combination. In this case report, we discussed a manic episode that developed after including trazodone for sleep problems in the treatment of a patient with an disorder who uses escitalopram.

Keywords: Anxiety disorders, mania, trazodone

Introduction

Available data indicate a high incidence of comorbidities between sleep problems and sev- eral mental illnesses, especially mood and anxiety disorders. Sleep-related symptoms, such as deterioration of sleep quality and continuity, cause advancement and exacerbation of psy- chiatric disorders. Similarly, these comorbidities may aggravate the diagnosis and treatment of the disorder.1 In clinical applications, sleep-adherent antidepressants, such as trazodone, , and , are commonly used. Moreover, mood dysregulation may oc- cur with different antidepressant combinations.2

Trazodone is a serotonin antagonist used in the treatment of depressive disorders ac- companied by anxiety and sleeping disorders and a well-tolerated antidepressant from the serotonin inhibitor group. It can be used as additional treat- ment in patients with psychiatric disorders who have sleep problems as hypnotic with H1 histamine antagonist effect.3, 4 Furthermore, it has been determined in a study that the usage of trazodone for sleep is a quarter of its usage as an antidepressant.5 After trazo- done intake, manic episode developed in two patients with bipolar and one patient with unipolar depression.6 In contrast, although it was indicated that there might be side effects, such as syndrome risks, when trazodone is used in combina- tion with selective serotonin (SSRI) and that when it is overdosed, pria- pism might occur; manic symptoms were not mentioned in case of SSRI intake.7 Although Filiz İzci the manic mechanism of trazodone is not fully known, it is accomplished with high doses Eda Ülger of serotonin reuptake inhibitor effect and 5HT2a blockade for its antidepressant activity.3 Sinem Yolcu We aimed to examine a manic episode that occurred after adding trazodone in the treatment Clinic of Psychiatry, Erenköy Mental and for sleep problems in a patient with who uses escitalopram. Neurological Disease Training and Research Hospital, İstanbul, Turkey Case Presentation Corresponding Author: A 72-year-old female patient with a diagnosis of anxiety disorder had been receiving her Filiz İzci  [email protected] treatment with 10 mg/day escitalopram for approximately two years. Approximately one Received: June 11, 2020 week ago, she was brought to our hospital for the complaint of increase in talking, decrease Accepted: July 17, 2020 in sleep, constant occupation with chores, constant interference in other household mem- Published Online: January 19, 2021 bers, not eating, making absurd and inappropriate jokes, and wandering off topic after Cite this article as: İzci F, Ülger E, Yolcu S. Manic Episode as a Result of Adding Copyright@Author(s) - Available online at alpha-psychiatry.com. Trazodone to a Patient under Escitalopram Content of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 Treatment. Alpha Psychiatry 2021;22(1):67- International License. 69.

67 Alpha Psychiatry 2021;22(1):67-69 İzci et al. Manic Episode as a Result of Adding Trazodone adding 50 mg/day trazodone to her present treatment in the epi- detected with a combination of SSRI and mirtazapine, which has a center. It was acknowledged that the patient had not had a similar hypnotic effect and are used with the purpose of toneup.10 In another history and a problem, had been able to do chores, did similar phenomenon, a maniac case has been reported in the case of not have an organic disease, and had no other regular treatment a combination of and mirtazapine.9 (other than escitalopram). It was noted that within two years, any hypomanic symptoms did not occur with the use of 10 mgescitalo- In our patient, manic episode was monitored after the addition of pram. In the mental status examination of the patient, her psycho- trazodone to the treatment of the patient using escitalopram who motor activity had increased, her speaking speed had increased, had an anxiety disorder and showed no kinds of mood episodes pre- her thought flow rate had increased, and her association of ideas viously. It is believed that the hypnotic effect of trazodone is revealed tended to loosen. Refusing to eat and drink, , and hostile under the influence of 5-HT2A and H1 histamine antagonist.11 More- and irritable behavior against frustration were detected. Psychotic over, it is indicated that trazodone promotes sleep continuity and content and suicidal thoughts were not identified. Her young ma- slow-wave sleep but has no impact on rapid-eye-movement sleep. It nia evaluation criteria point was 25. Her routine complete blood has been observed that trazodone induced manic switches in a few cell count, biochemical parameters, and thyroid hormone profile cases so far.8 In addition, the mania induced by trazodone occurred tests were normal. She was suggested to stay in the hospital with at 50-400 mg/day range. This is a low risk for switch to mania during the prediagnosis of manic episode derived from drug usage and treatment with sleep-promoting antidepressants.12 In our patient, induced by trazodone. Because the patient and her relatives did not manic episode was developed after 1 week of treatment with 50 mg/ agree with inpatient treatment, her existing treatment was discon- day trazodone. In the instance of mania phenomenon developing tinued, and she was expected to check in daily for patient follow-up with a combination of SSRI and trazodone, it has been indicated that with the treatment of 10 mg/day and 2.5 mg/day lora- trazodone induced mania by increasing the serum concentration of zepam. Her relatives were informed about her disorder. On the 5th .2 day of the patient’s follow-up with her present treatment, it was determined that her mood was euthymic, her psychomotor activity Manic switches were observed while using antidepressants as mono- was reduced, her sleep and regulations were stable, and therapy in patients who are bipolar in the clinic.13 In particular, manic her associations and thought content were normal. The patient’s shifts have been shown to be more associated with antide- treatment was minimized, and she was called for a fol- pressants and specific serotonin and noradrenaline reuptake inhibi- low-up in 10 days. In addition, written consent was obtained from tors. Although some possible mechanisms have been proposed, the the patient to publish this information. exact mechanisms for mood swings are still uncertain.14, 15

Discussion In a study in which trazodone, mirtazapine, and agomelatine were used in low doses for their hypnotic effects, a switch was only ob- The effects of an antidepressant on sleep have a crucial role to play served in patients with the risk of manic switch. It was indicated in its clinical usage. For a quick recovery in sleep quality, this group that low doses of trazodone and mirtazapine should be safe and of is indicated, especially in patients with depression that they can be used as an important alternative to in who have insomnia, anxiety, agitation, and suicidal thoughts. In a sleep deprivation treatment. It has been mentioned that these an- study that compared the effects of trazodone on sleep in patients tidepressants can confidently be used when taken with a mood who are depressive with agomelatine, , , stabilizer.12 Moreover, despite having no bipolar history and no , and mirtazapine, it was monitored that adding low dos- mood episodes while taking escitalopram regularly for two years, ages of these medications that have a -like characteristic to it must not be ignored that additional sleep deprivation might be the treatment becomes a preventer against hypnotic addiction and the beginning of a manic stage. However, in our phenomenon, no treats agitation, anxiety, or sleep deprivation.8 risk factor causing a tendency to bipolarity was defined. In addition, With antidepressant usage, in addition to the possibility of inducing after stopping trazodone, the patient’s manic symptoms improved. manic episodes, it may cause manic switches in patients with de- Therefore, we believe that mania was induced after the usage of pression. Manic episodes resulting from antidepressants have been trazodone. identified related to tricyclic antidepressants, inhibitors, SSRI, , and mirtazapine.9 Similar to our patient, In conclusion, even in patients without bipolar history and tenden- manic episodes may occur with antidepressants along with other cy, it must not be neglected that additional antidepressants with the groups of antidepressants. Accordingly, manic switches have been purpose of taking advantage of their hypnotic effects or using them as a tone-up might cause manic switches during another antidepres- MAIN POINTS sant treatment. It must not be ignored that an antidepressant with a hypnotic effect, such as trazodone, which is included in the treat- • Escitalopram and trazodone combination therapy can increase ment for sleep problems, might induce a manic episode. Potential the risk of inducing mania. risks in terms of manic induction must be deeply evaluated. • If a second antidepressant is added to the treatment in individuals without a history of , awareness of manic shift will be important. • The use of trazodone in elderly individuals creates a risk of induc- Informed Consent: Informed consent was obtained from the patient who partic- ing mania or , even at low doses, due to decreased ipated in this study. elimination rates. Peer-review: Externally peer-reviewed.

68 İzci et al. Manic Episode as a Result of Adding Trazodone Alpha Psychiatry 2021;22(1):67-69

Author Contributions: Concept - F.İ.; Design - F.İ.; Supervision - F.İ.; Resources - F.İ.; 7. Prapotnik M, Waschgler R, König P, et al. Therapeutic drug monitoring of Materials - E.Ü., S.Y.; Data Collection and/or Processing - E.Ü., S.Y.; Analysis and/or trazodone: are there pharmacokinetic interactions involving Interpretation - E.Ü., S.Y.; Literature Search - F.İ.; Writing Manuscript - F.İ.; Critical and fluoxetine?Int J Clin Pharmacol Ther. 2004;42(2):120-124. [Crossref] Review - F.İ., E.Ü., S.Y. 8. Wichniak A, Wierzbicka A. The effects of antidepressants on sleep in de- pressed patients with particular reference to trazodone in comparison Conflict of Interest: The authors have no conflict of interest to declare. to agomelatine, amitriptyline, doxepin, mianserine and mirtazapine. Pol Merkur Lekarski. 2011;31(181):65-70. Financial Disclosure: The authors declared that this study has received no finan- 9. Bernardo NG. Mania associated with mirtazapine aug-mentation of flu- cial support. oxetine. Depress Anxiety. 2002;15(1):46-47. [Crossref] References 10. Liu CC, Liang KY, Liao SC. Antidepressant-associated mania: soon after switch from fluoxetine to mirtazapine in an elderly woman with mixed 1. Satetia MJ. Update on sleep and psychiatric disorders. Chest. depressive features. J Psychopharmacol. 2009;23(2):220-222. [Crossref] 2009;135(5):1370-1379. [Crossref] 11. Wichniak A, Wierzbicka A, Jernajczyk W. Sleep and antidepressant treat- 2. Hu J, Lai J, Zheng H, et al. Fan the flame: trazo-done-induced mania in a ment. Curr Pharm Des. 2012;18(36):5802-5817. [Crossref] unipolar depressed patient with stable sertraline treatment. Neuropsy- 12. Wichniak A, Jarkiewicz M, Okruszek Ł, et al. Low risk for switch to mania chiatr Dis Treat. 2017;13:2251-2254. [Crossref] during treatment with sleep promoting antidepressants. Pharmacopsy- 3. Stahl SM. Mechanism of action of trazodone: a multi-functional drug. chiatry. 2015;48(3):83-88. [Crossref] CNS Spectr. 2009;14(10):536-546. [Crossref] 13. Baldessarini RJ, Faedda GL, Offidani E, et al. Antidepressant-associated 4. Fagiolini A, Comandini A, Dell’Osso MC, et al. Rediscovering trazo- mood-switching and transition from unipolar major depression to bipo- done for the treatment of major depressive disorder. CNS Drugs. lar disorder: a review. J Affect Disord. 2013;148(1):129-135. [Crossref] 2012;26(12):1033-1049. [Crossref] 14. Koszewska I, Rybakowski JK. Antidepressant-induced mood conversions 5. Wong J, Motulsky A, Abrahamowicz M, et al. Off label indications for anti-de- in bipolar disorder: a retrospective study of tricyclic versus non-tricyclic pressants in primary care: descriptive study of pre-scripttions from an indi- antidepressant drugs. Neuropsychobiology. 2009;59(1):12-16. [Crossref] cation based electronic prescribing system. BMJ. 2017;356:j603. [Crossref] 15. Post RM, Altshuler LL, Leverich GS, et al. Mood switch in bipolar depres- 6. Knobler HY, Itzchaky S, Emanuel D, et al. Trazodone-induced mania. Br J sion: comparison of adjunctive , buproprion and sertraline. Psychiatry. 1986;149:787-789. [Crossref] Br J Psychiatry. 2006;189(2):124-131. [Crossref]

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